Cyclophosphamide suivi d'une perfusion intraveineuse et intrapéritonéale de lymphocytes T autologues génétiquement modifiés pour sécréter l'IL-12 et cibler l'antigène MUC16ecto chez les patients atteints de tumeurs solides récurrentes MUC16ecto+

Inclusion Criteria:

• Pathologically confirmed diagnosis of high-grade serous ovarian, primary peritoneal, or fallopian tube carcinoma
• Presence of measurable recurrence, with RECIST measurable disease at the time of intervention consent
• Patient's carcinoma must express the MUC16ecto antigen detectable by IHC analysis of banked (paraffin embedded) or freshly biopsied tumor
• IHC evidence of MUC16ecto expression will be performed according to the technique and 0-5 scoring system described by Dharma et al (63)
• Only MUC16ecto tumors with moderate to strong immunoreactive scores (3-5) will be considered positive
• Patients must have had one prior platinum-based chemotherapeutic regimen for management of ovarian, primary peritoneal, or fallopian tube carcinoma and at least two prior chemotherapy regimens.
• Patients are allowed to receive, but are not required to receive, up to 5 additional prior chemotherapy treatment regimens (including platinum-based chemotherapy). Prior hormonal therapy is allowed, does not count towards this prior regimen requirement, and must be discontinued at least one week prior to T cell infusion. Continuation of hormone replacement therapy is permitted
• Patients are allowed to receive, but are not required to receive, biologic/targeted therapy as part of their primary treatment regimen. Patients are allowed to receive, but are not required to receive, up to 5 biologic/targeted therapies as part of their treatment regimen for recurrent disease (either alone or in combination with chemotherapy)
• Karnofsky Performance Status score of 70% or greater
• Life expectancy of at least 3 months
• Adequate bone marrow, renal, and hepatic function:
• Absolute neutrophil count (ANC) ≥ 1500/mm³
• Platelets ≥ 100,000/mm³
• Creatinine ≤ 1.5mg/dL or creatinine clearance > 60ml/min
• ALT, AST, and total bilirubin all < 2.5 x the institutional upper limit of normal (ULN)
• Adequate pulmonary and cardiac function: No clinical evidence of cardiopulmonary disease, which, in the opinion of the investigator, precludes enrollment
• Age ≥18 years
• No anti-cancer therapy (chemotherapy, biologic therapy, or immunotherapy) in the 3 weeks prior to the T cell infusion (and all hematologic effects have resolved). No prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or CTL4-antagonist or similar agent) in the 6 months prior to the T cell infusion (and all clinically significant related side-effects related must be resolved).

Exclusion Criteria:

• Known active hepatitis B infection, known history of hepatitis C or HIV infection
• Clinical or radiographic evidence of bowel obstruction, or need for parenteral hydration and/or nutrition
• Known or suspected extensive abdominal adhesions.
• Any of the following cardiac conditions:
• Clinically significant heart disease (NYHA class III or IV) or symptomatic congestive heart failure
• Myocardial infarction ≤6 months prior to enrollment
• History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
• History of severe non-ischemic cardiomyopathy with ejection fraction ≤20%
• Active autoimmune disease (excluding autoimmune thyroid disease on a stable thyroid regimen). Such conditions include but are not limited to systemic lupus erythematous, rheumatoid arthritis, ulcerative colitis, Crohn's disease and temporal arteritis.
• Known or suspected leptomeningeal disease; patients with metastases to the brain stem, midbrain, pons or medulla.
• Known or suspected untreated brain metastases. Patients with Radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is ≥4weeks beyond completion of cranial irradiation and ≥ 3 weeks off of corticosteroid therapy at the time of study intervention.
• Prior history of seizure disorder
• Any concurrent active malignancies, defined as malignancies requiring any therapy other than expectant observation, since adverse events resulting from these malignancies or their treatment may confound our assessment of the safety of adoptive T cell therapy for ovarian cancer.
• Prior radiotherapy to any portion of the abdominal cavity or pelvis
• Current pregnancy or lactation
• Any of the following within 28 days of first date of study treatment:
• Serious uncontrolled medical illness or disorder that in the opinion of the treating physician would make the patient ineligible for the study
• Active uncontrolled infection (with the exception of uncomplicated urinary tract infection)
• Abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
• Abdominal surgery (for reasons other than IP port placement)
• Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study